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Clin Cancer Res. 2008 Aug 1;14(15):4935-42. doi: 10.1158/1078-0432.CCR-08-0958.

Suppression of tumor formation by a cyclooxygenase-2 inhibitor and a peroxisome proliferator-activated receptor gamma agonist in an in vivo mouse model of spontaneous breast cancer.

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1
Authors' Affiliation: Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Abstract

PURPOSE:

Activation of COX-2 and inhibition of PPARgamma have been observed in human and animal models of breast cancer. Both inhibition of COX-2 and activation of PPARgamma can inhibit proliferation of breast cancer cells in vitro. Here, we examine the effects of the COX-2 inhibitor celecoxib and the PPARgamma agonist N-(9-fluorenyl-methyloxycarbonyl)-l-leucine (F-L-Leu) on mouse breast tumor cells in vitro and in vivo.

EXPERIMENTAL DESIGN:

We created and characterized a mouse mammary adenocarcinoma cell (MMAC-1) line from C3 (1)-SV40 tumor antigen mice to study COX-2 and PPARgamma expression and response to celecoxib and F-L-Leu in vitro. To study the in vivo effects, C3 (1)-SV40 tumor antigen mice were given either control diet or diets containing three different concentrations of celecoxib and F-L-Leu as well as a combination of both agents. Mice were then followed for tumor formation up to 1 year.

RESULTS:

MMAC-1 cells express both COX-2 and PPARgamma mRNA and exhibited cooperative growth inhibition with a combination of celecoxib and F-L-Leu. In mice, the median age of death due to mammary tumors was significantly delayed in celecoxib-treated animals at all three concentrations but was not significantly affected by F-L-Leu treatment alone. A combination of celecoxib and F-L-Leu was significantly more effective than celecoxib alone.

CONCLUSIONS:

Our findings suggest that a combination of a COX-2 inhibitor and PPARgamma agonist can delay breast cancer in a mouse model and suggest that these agents should be studied in the context of human populations with high breast cancer risk.

PMID:
18676768
PMCID:
PMC2587271
DOI:
10.1158/1078-0432.CCR-08-0958
[Indexed for MEDLINE]
Free PMC Article
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